Xiuju Peng

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment. In preclinical investigations, combined effect of certain known drugs has been well established in treating extensive human diseases. Attributed to synergistic effects by targeting various disease pathways and advantages, such as reduced administration dose, decreased toxicity, and alleviated drug resistance, combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses, such as cancer, atherosclerosis, pulmonary hypertension, myocarditis, rheumatoid arthritis, inflammatory bowel disease, metabolic disorders and neurodegenerative diseases. Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease. Nanoparticle (NP)-mediated drug delivery systems, i.e., liposomal NPs, polymeric NPs and nanocrystals, are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery, extended drug release, and higher drug stability to avoid rapid clearance at infected areas. This review summarizes various targets of diseases, preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases. Ultimately, we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations. This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.

Biologics have low toxicity and are highly specific and biocompatible, offering advantages over small-molecule drugs. The administration of biologics in oral form provides a significant benefit in improving patient compliance. However, oral administration faces the challenge of a harsh gastrointestinal environment, including low pH, enzyme degradation, and poor intestinal epithelium permeability, which limits the bioavailability of biologics. As a result, the administration of biologics remains primarily in the parenteral form. This review introduces the physiological barriers encountered by oral biologics delivery, describes the oral biologics currently on the market or under clinical trials, as well as oral biologics-based technologies, and discusses the recent progress on novel oral delivery technologies such as nanoparticle-delivery systems, ionic liquids, and microneedles. Specifically, colon-targeted approaches for oral biologics delivery are also explored, as the colon could be a more optimal absorption site due to having less diverse proteolytic enzymes and relatively limited digestibility compared to the upper gastrointestinal tract (GIT). Lastly, the future research directions for oral biologics are highlighted and it is concluded that with an in-depth study of biological drugs and advancement in delivery methods, oral biologics can pioneer new opportunities.